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Chuigong Yu,
Guojun Wu,
Nana Dang,
Wei Zhang, Rui Zhang,
Wei Yan,
Yi Zhao,
Lei Gao,
Yingmei Wang,
Noor Beckwith,
Jianlin Yuan,
Libo Yao
[show abstract]
[hide abstract]
ABSTRACT: To study the expression of N-myc Downstream Regulated Gene-2 (NDRG2) in prostatic carcinoma (PCA) tissue and in different PCA cell lines, and to investigate its clinical and pathological implications, 144 PCA and benign prostatic hyperplasia (BPH) tissue sections were analyzed retrospectively with immunohistochemistry (S-P method). The expression levels of NDRG2 and c-Myc in prostate cell lines were detected through Western blot. The effects of adenovirus-mediated NDRG2 on PC3 cells and PC3 nude mouse xenografts was observed through cell growth curves, tumor growth curves, flow cytometry (FCM), transmission electron microscopy (TEM) and TUNEL staining. The NDRG2 gene was highly expressed in BPH tissues, but not in carcinomatous ones (χ(2)=25.98, p < 0.001). Furthermore, positive expression of NDRG2 was negatively correlated with the Gleason score (r = -0.445, p< 0.001) and the c-myc level (r = -0.311, p < 0.001). However, positive expression of NDRG2 was not correlated with pTNM tumor stages or the serum concentration of prostate-specific antigen (PSA) (p > 0.05). The expression of the NDRG2 genes was low in the three PCA cell lines. PC3 cells infected by pAD-cmv-NDRG2 showed inhibition of proliferation both in vitro and vivo. To sum up, NDRG2 may be involved in the carcinogenesis and progression of PCA. Moreover, adenovirus-mediated NDRG2 can suppress the proliferation of PC3 cells significantly both in vitro and in vivo. These results indicate that NDRG2 may become a new target gene for PCA diagnosis and therapy.
Cancer biology & therapy 08/2011; 12(4):304-13. · 2.64 Impact Factor
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Jin Zheng,
Yan Li,
Jiandong Yang,
Qiang Liu,
Ming Shi, Rui Zhang,
Hengjun Shi,
Qinyou Ren,
Ji Ma,
Hang Guo,
Yurong Tao,
Yan Xue,
Ning Jiang,
Libo Yao,
Wenchao Liu
[show abstract]
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ABSTRACT: The prognosis of most hepatocellular carcinoma (HCC) patients is poor due to the high metastatic rate of the disease. Understanding the molecular mechanisms underlying HCC metastasis is extremely urgent. The role of CD24 and NDRG2 (N-myc downstream-regulated gene 2), a candidate tumor suppressor gene, has not yet been explored in HCC.
The mRNA and protein expression of CD24 and NDRG2 was analyzed in MHCC97H, Huh7 and L-02 cells. Changes in cell adhesion, migration and invasion were detected by up- or down-regulating NDRG2 by adenovirus or siRNA. The expression pattern of NDRG2 and CD24 in HCC tissues and the relationship between NDRG2 and HCC clinical features was analyzed by immunohistochemical and western blotting analysis.
NDRG2 expression was negatively correlated with malignancy in HCC. NDRG2 exerted anti-tumor activity by regulating CD24, a molecule that mediates cell-cell interaction, tumor proliferation and adhesion. NDRG2 up-regulation decreased CD24 expression and cell adhesion, migration and invasion. By contrast, NDRG2 down-regulation enhanced CD24 expression and cell adhesion, migration and invasion. Immunohistochemical analysis of 50 human HCC clinical specimens showed a strong correlation between NDRG2 down-regulation and CD24 overexpression (P = 0.04). In addition, increased frequency of NDRG2 down-regulation was observed in patients with elevated AFP serum level (P = 0.006), late TNM stage (P = 0.009), poor differentiation grade (P = 0.002), tumor invasion (P = 0.004) and recurrence (P = 0.024).
Our findings indicate that NDRG2 and CD24 regulate HCC adhesion, migration and invasion. The expression level of NDRG2 is closely related to the clinical features of HCC. Thus, NDRG2 plays an important physiological role in HCC metastasis.
BMC Cancer 06/2011; 11:251:1-9. · 3.01 Impact Factor
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Lan Shen,
Xuewu Liu,
Wugang Hou,
Guodong Yang,
Yousheng Wu, Rui Zhang,
Xia Li,
Honglei Che,
Zifan Lu,
Yuanqiang Zhang,
Xinping Liu,
Libo Yao
[show abstract]
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ABSTRACT: The N-myc downstream-regulated gene 2 (NDRG2) is involved in cell differentiation and apoptosis, but its function in the pancreas remains to be established. Herein we examine the expression and function of NDRG2 in the endocrine pancreas. NDRG2 immunoreactivity was localized mainly in the cytoplasm of pancreatic beta cells. When beta-TC3 cells were exposed chronically to high levels of free fatty acid (FFA), cell viability was impaired, and Akt and NDRG2 phosphorylation were reduced. NDRG2 is a potential substrate of protein kinase Akt. Overexpression of constitutively active Akt enhanced NDRG2 phosphorylation and abolished the apoptosis induced by FFA in beta-TC3 cells, whereas NDRG2 knock-down attenuated Akt-mediated protection of beta cells against fatty acid-triggered apoptosis. Collectively, these data indicate that NDRG2 acts as a key molecule in pancreatic beta cells and is involved in the Akt-mediated protection of beta cells against lipotoxicity.
Cellular and Molecular Life Sciences CMLS 04/2010; 67(8):1371-81. · 6.57 Impact Factor
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Jin Zheng,
Qiang Liu,
Yan Li,
Jiandong Yang,
Ji Ma,
Fang Yu,
Hengjun Shi,
Qinyou Ren, Rui Zhang,
Jin Zhang,
Yan Xue,
Yurong Tao,
Ning Jiang,
Hang Guo,
LiBo Yao,
Wenchao Liu
[show abstract]
[hide abstract]
ABSTRACT: Breast cancer is the most common malignancy in women in the world. High incidence and poor clinical outcomes underly the need for a better understanding of its tumor biology and how to effectively inhibit tumor progression. In the present study the question of whether NDRG2 might be a useful target for breast cancer therapy was addressed. With the increase or decrease of NDRG2 levels in MCF-7 and Bcap-37 cells by adenovirus-NDRG2 infection or NDRG2 siRNA transfection, CD24 expression was significantly decreased or increased, respectively. Furthermore, NDRG2 overexpression suppressed breast cancer cell adhesion and invasion, whereas knockdown of NDRG2 promoted these events. In conclusion, the data from the current study indicated that NDRG2, the product of a tumor suppressor gene, can regulate CD24 expression to decrease the metastatic potential of breast cancer cells.
Asian Pacific journal of cancer prevention: APJCP 01/2010; 11(6):1817-21. · 0.66 Impact Factor
